Sanne K Meles

Abnormal metabolic pattern associated with cognitive impairment in Parkinson's disease : a validation study

Cognitive deficits in Parkinsons disease (PD) have been associated with a specific metabolic covariance pattern. Although the expression of this PD cognition-related pattern (PDCP) correlates with neuropsychological performance, it is not known whether the PDCP topography is reproducible across PD populations. We therefore sought to identify a PDCP topography in a new sample comprised of 19 Dutch PD subjects. Network analysis of metabolic scans from these individuals revealed a significant PDCP that resembled the original network topography. Expression values for the new PDCP correlated (P = 0.001) with executive dysfunction on the Frontal Assessment Battery (FAB). Subject scores for the new PDCP correlated (P < 0.001) with corresponding values for the original pattern, which also correlated (P < 0.005) with FAB scores in this patient group. For further validation, subject scores for the new PDCP were computed in an independent group of 86 American PD patients. In this cohort, subject scores for the new and original PDCP topographies were closely correlated (P < 0.001); significant correlations between pattern expression and cognitive performance (P < 0.05) were observed for both PDCP topographies. These findings suggest that the PDCP is a replicable imaging marker of PD cognitive dysfunction.

Metabolic Imaging in Parkinson Disease

This review focuses on recent human 18F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how 18F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of 18F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed.

FDG PET, Dopamine Transporter SPECT, and Olfaction: Combining Biomarkers in REM Sleep Behavior Disorder

Idiopathic REM sleep behavior disorder is a prodromal stage of Parkinsons disease and dementia with Lewy bodies. Hyposmia, reduced dopamine transporter binding, and expression of the brain metabolic PD‐related pattern were each associated with increased risk of conversion to PD. The objective of this study was to study the relationship between the PD‐related pattern, dopamine transporter binding, and olfaction in idiopathic REM sleep behavior disorder.

The metabolic pattern of idiopathic REM sleep behavior disorder reflects early-stage Parkinson's disease

Idiopathic REM sleep behavior disorder (iRBD) is considered a prodromal stage of Parkinson disease (PD) and other Lewy body disorders. Spatial covariance analysis of 18F-FDG PET data has disclosed a specific brain pattern of altered glucose metabolism in PD. In this study, we identify the metabolic pattern underlying iRBD and compare it with the known PD pattern. To understand the relevance of the iRBD pattern to disease progression, we studied the expression of the iRBD pattern in de novo PD patients. Methods: The iRBD-related pattern was identified in 18F-FDG PET scans of 21 patients with polysomnographically confirmed iRBD and 19 controls using spatial covariance analysis. Expression of the iRBD-related pattern was subsequently computed in 18F-FDG PET scans of 44 controls and 38 de novo, treatment-naïve PD patients. Of these 38 PD patients, 24 had probable REM sleep behavior disorder (RBD) according to the Mayo Sleep Questionnaire. Neuropsychologic evaluation showed mild cognitive impairment in 20 PD patients (PD-MCI), of whom 16 also had concomitant RBD and roughly half (11/20) had bilateral motor symptoms. Results: The iRBD-related pattern was characterized by relative hypermetabolism in the cerebellum, brain stem, thalamus, sensorimotor cortex, and hippocampus, and by relative hypometabolism in the middle cingulate, temporal, occipital, and parietal cortices. This topography partially overlapped with the PD-related pattern (PDRP). The iRBD-related pattern was significantly expressed in PD patients compared with controls (P < 0.0001). iRBD-related pattern expression was not significantly different between PD patients with and without probable RBD, or between PD patients with unilateral or bilateral parkinsonism. iRBD-related pattern (iRBDRP) expression was higher in PD-MCI patients than in PD patients with preserved cognition (P = 0.001). Subject scores on the iRBD-related pattern were highly correlated to subject scores on the PDRP (r = 0.94, P < 0.0001). Conclusion: Our results show that the iRBDRP is an early manifestation of the PDRP. Expression of both PDRP and iRBDRP was higher in patients with a more severe form of PD (PD-MCI), which indicates that expression of the 2 patterns increases with disease severity.

The Alzheimer’s disease metabolic brain pattern in mild cognitive impairment

We investigated the expression of the Alzheimer’s disease-related metabolic brain pattern (ADRP) in 18F-FDG-PET scans of 44 controls, 27 patients with mild cognitive impairment (MCI) who did not convert to Alzheimer’s disease (AD) after five or more years of clinical follow-up, 95 MCI patients who did develop AD dementia on clinical follow-up, and 55 patients with mild-to-moderate AD. The ADRP showed good sensitivity (84%) and specificity (86%) for MCI-converters when compared to controls, but limited specificity when compared to MCI non-converters (66%). Assessment of 18F-FDG-PET scans on a case-by-case basis using the ADRP may be useful for quantifying disease progression.

Dual time point method for the quantification of irreversible tracer kinetics: A reference tissue approach applied to [18F]-FDOPA brain PET.

The Patlak graphical analysis (PGAREF) for quantification of irreversible tracer binding with a reference tissue model was approximated by a dual time point imaging approach (DTPREF). The DTPREF was applied to 18 [18F]-FDOPA brain scans using the occipital cortex as reference region (DTPOCC) and compared to both PGAOCC and striatal-to-occipital ratios (SOR). Pearson correlation analysis and Bland–Altman plots showed an excellent correlation and good agreement between DTPOCC and PGAOCC, while correlations between SOR and PGAOCC were consistently lower. Linear discriminant analysis (LDA) demonstrated a similar performance for all methods in differentiating patients with Parkinson’s disease (PD) from healthy controls (HC). Specifically for [18F]-FDOPA brain imaging, these findings validate DTPOCC as an approximation for PGAOCC, providing the same quantitative information while reducing the acquisition time to two short static scans. For PD patients, this approach can greatly improve patient comfort while reducing motion artifacts and increasing image quality. In general, DTPREF can improve the clinical applicability of tracers with irreversible binding characteristics when a reference tissue is available.

Brain Imaging in RBD

Neuroimaging studies can provide in vivo insights to the early structural and functional brain changes in patients with idiopathic RBD (iRBD) and may help give a prognosis of disease course. This chapter summarizes the major findings of neuroimaging studies in iRBD, a specific prodromal stage of Parkinson’s disease (PD) and other α-synucleinopathies. Molecular imaging techniques, magnetic resonance imaging (MRI), and transcranial sonography (TCS) are all discussed.